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Updated: Jul 6, 2025
Optimized Management of Endovascular Treatment for Acute Ischemic Stroke
Published on: January 18, 2018
Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke
Ying Gao1, Weiqi Chen1, Yuesong Pan1
1From the Department of Neurology, Beijing Tiantan Hospital (Y.G., W.C., Y.P., J.J., C.W., Y.Y., T.W., S.H., X.M., X.Z., L.L., Yongjun Wang, Yilong Wang), the Advanced Innovation Center for Human Brain Protection (Yongjun Wang, Yilong Wang), Beijing Laboratory of Oral Health (Yilong Wang), and Beijing Municipal Key Laboratory of Clinical Epidemiology (Yilong Wang), Capital Medical University, the China National Clinical Research Center for Neurological Diseases (Y.P., J.J., C.W., L.J., X.M., J.L., X.Z., L.L., Yongjun Wang, Yilong Wang), the National Center for Neurological Disorders (Yongjun Wang, Yilong Wang), the Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences (Yongjun Wang), and the Chinese Institute for Brain Research (Yilong Wang), Beijing, the Department of Neurology, Weihai Wendeng District People's Hospital, Weihai (J.Z.), the Department of Neurology, Sui Chinese Medical Hospital, Shangqiu (Y.L.), the Department of Neurology, Qinghe People's Hospital, Xingtai (Y.Z.), the Department of Neurology, Biyang People's Hospital, Zhumadian (S.Z.), the Department of Neurology, Jiyuan Chinese Medical Hospital, Jiyuan (H.Y.), the Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an (J.Y.), the Department of Neurology, Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian (Yuanwei Wang), the Department of Neurology, Mengzhou People's Hospital (D. Li), and the Department of Neurology, Xiuwu People's Hospital (G.K.), Jiaozuo, and the Department of Neurology, Hejian People's Hospital, Cangzhou (Yanxia Wang, D. Liu) - all in China; the Department of Neurology, University of California, San Francisco, San Francisco (S.C.J.); the Department of Neurology and Stroke Center, Assistance Publique-Hôpitaux de Paris, Bichat Hospital, INSERM Laboratory for Vascular Translational Science-Unité 1148, University of Paris, Paris (P.A.); the Population Health Research Institute, McMaster University, Hamilton, ON, Canada (P.A.); and the Stroke Trials Unit, Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom (P.M.B.).
Insights
Dual antiplatelet therapy with clopidogrel and aspirin, initiated within 72 hours of acute ischemic stroke, reduced recurrent stroke risk compared to aspirin alone. However, this combination therapy slightly increased the risk of moderate-to-severe bleeding.
Area of Science:
- Neurology
- Cardiology
- Pharmacology
Background:
- Dual antiplatelet therapy (clopidogrel plus aspirin) shows promise in reducing recurrent stroke risk when started early after acute mild stroke.
- The efficacy and safety of clopidogrel plus aspirin versus aspirin alone, when administered within 72 hours of acute cerebral ischemia due to atherosclerosis, remain understudied.
Purpose of the Study:
- To evaluate the effectiveness of clopidogrel plus aspirin compared to aspirin alone in preventing new strokes within 90 days.
- To assess the safety profile, specifically the incidence of moderate-to-severe bleeding, associated with this dual antiplatelet therapy.
Main Methods:
- A double-blind, randomized, placebo-controlled trial was conducted in 222 Chinese hospitals.
- 6100 patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of atherosclerotic origin were randomized within 72 hours of symptom onset.
- Patients received either clopidogrel plus aspirin or clopidogrel placebo plus aspirin, with outcomes assessed at 90 days.
Main Results:
- The clopidogrel-aspirin group experienced a new stroke in 7.3% of patients, versus 9.2% in the aspirin-only group (hazard ratio, 0.79; P=0.008).
- Moderate-to-severe bleeding occurred in 0.9% of the clopidogrel-aspirin group compared to 0.4% in the aspirin group (hazard ratio, 2.08; P=0.03).
Conclusions:
- Initiating combined clopidogrel-aspirin therapy within 72 hours of mild ischemic stroke or high-risk TIA significantly lowers the risk of recurrent stroke at 90 days.
- While effective, this dual therapy is associated with a small but statistically significant increase in the risk of moderate-to-severe bleeding.
Background:
Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied.
Methods:
In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days.
Results:
A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03).
Conclusions:
Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).
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